US4269851A - 8-Aminoalkyl-4-alkylpsoralens - Google Patents
8-Aminoalkyl-4-alkylpsoralens Download PDFInfo
- Publication number
- US4269851A US4269851A US06/073,907 US7390779A US4269851A US 4269851 A US4269851 A US 4269851A US 7390779 A US7390779 A US 7390779A US 4269851 A US4269851 A US 4269851A
- Authority
- US
- United States
- Prior art keywords
- aminomethylpsoralen
- compound
- methyl
- mmol
- activity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
Definitions
- Psoralens, photochemotherapy, psoralens having enhanced photosensitizing activity for use in photochemotherapy are preferred.
- Psoralens have been used for years as dermalphotosensitizing agents, e.g., in the treatment of vitiligo. Their topical and/or oral application, followed by irradiation with light, results in stimulation of melanin, thus producing a tanning effect. They have accordingly also been used for such cosmetic purpose. More recently, psoralens have been found useful in the photochemotherapeutic treatment of psoriasis, in which case they are administered orally or topically to the subject, whose skin is subsequently exposed to controlled ultraviolet radiation, as in a Psoralite (TM) apparatus. A high percentage of remissions of this disease have been effected in such manner.
- TM Psoralite
- the photosensitization effect does not decline relatively rapidly, or at least within a reasonably limited period after maximization, a patient must be confined for uneconomic and undesirable periods after treatment so that photosensitization does not continue after the desired ultraviolet light treatment period, with the distinct danger of excessive and undesirable continuance of photochemotherapy because of exposure to normally-encountered light rays upon leaving the treatment area.
- the criteria of rapid onset, early maximization, and rapid decline of photosensitization effect have already become established as desirable criteria for the photosensitizing agent in this relatively new but rapidly-expanding field of photochemotherapy, certainly of equal importance as contrasted to the single previously-important criterion of high maximum photosensitization activity alone.
- psoralens such as trimethylpsoralen (4,5', 8-trimethylpsoralen or trioxsalen) are characterized by considerable topical activity, they have a diminished order of oral activity, or at least the oral activity is a modicum for purposes of practical photochemotherapeutic utilization. In contrast, 8-methoxypsoralen is characterized by significant oral activity.
- trimethylpsoralen 4,5', 8-trimethylpsoralen or trioxsalen
- 8-methoxypsoralen is characterized by significant oral activity.
- 4,124,598 and 4,130,568 are also characterized structurally by the presence of an 8 carbon atom substituent, e.g., an 8-methoxy or 8-methyl substituent, which has heretofore apparently been considered desirable for substantial photosensitizing activity, whether oral or topical of course along with other substituents present in the 4',4, and 5' positions, in those prior art psoralen compounds which have heretofore been found to have desired photochemotherapeutic activity.
- an 8 carbon atom substituent e.g., an 8-methoxy or 8-methyl substituent
- the present invention relates to 8-aminoalkyl-4-alkylpsoralens having enhanced photosensitizing activity, especially oral activity, including early onset, increased maximum, and rapid decline, as well as low toxicity, when compared with psoralens of different structure. It is particularly concerned with 4-loweralkyl-8-primaryaminoloweralkylpsoralens, particularly 4-loweralkyl-8-aminomethylpsoralens, and especially 4-methyl-8-aminomethylpsoralen.
- the compounds of this invention have no 8 carbon atom methyl or methoxy substituent as in the prior art compounds trisoralen (4,5',8-trimethylpsoralen), 8-methoxypsoralen, or the compounds of U.S. Pat. Nos. 4,124,598 or 4,130,568. No. 4' or 5' carbon atom substituent is essential, as in U.S. Pat. No. 4,124,598.
- An 8-aminoloweralkyl group is uniquely present, however, which is absent from all the aforementioned reference compounds.
- the compounds of the invention have the formula: ##STR1## 4-loweralkyl-8-primaryaminoloweralkylpsoralen, wherein loweralkyl is preferably methyl.
- That material (3.127 g, 13.64 mmol) was recrystallized from a benzene: ligroin (EK-P 1628)::80 ml:40 ml, solvent mixture to obtain pure 4-methyl-8-aminomethylpsoralen (1.61 g, 7.02 mmol, 44%), mp 154°-156° C.
- loweralkyl comprehends such straight or branched radicals or groups having one to eight carbon atoms, preferably one to four carbon atoms, inclusive, such as methyl, ethyl, propyl, isopropyl, butyl, and the like.
- the 8-aminomethylpsoralen was made in the same manner, starting from 8-methylpsoralen, a known compound, for comparison purposes.
- the final step of its preparation follows:
- 8-Aminomethylpsoralen A mixture of 8-phthalimidomethylpsoralen (0.250 g, 0.724 mmol), 95% ethanol (31 mL), glacial acetic acid (0.66 mL, 11.6 mmol), and 85% hydrazine hydrate (0.33 mL, 5.79 mmol) was refluxed with stirring (magnetic) until all of the phthalimidopsoralen had dissolved and until a TLC monitor showed the absence of starting material (ca. 33/4hours). The solution was concentration in vacuo to a viscous yellow liquid, which was acidified with 1 N aq.
- the biophotosensitization activity of the compounds of the present invention was determined by visual grading of erythemal response according to a modification of the procedure of Pathak and Fitzpatrick, J. Invest. Dermatol. 32, 509-518 (1959), entitled "Bioassay of Natural and Synthetic Furocoumarins (Psoralens)".
- the psoralens are of course "linear” isomers of the furocoumarin family.
- erythema production on albino guinea pig skin is measured visually and the response accorded a gradation definition according to 0, ⁇ , 1, 2, 3, and 4 scale.
- the modification employed involved variation of the time between administration of the test compound and exposure to ultraviolet light, thereby enabling measurement of times of onset and decline of the induced photosensitivity effect.
- Topical Each drug is tested topically at a concentration of one percent (1%) in ethanolic solution. Test sites of one square centimeter of skin each receive one-tenth milliliter of a particular selected test solution thirty minutes prior to exposure to three joules of ultraviolet "A" radiation. Three species of fifteen in each group of guinea pigs are tested with each product to arrive at an average response designated “Reaction Intensity,” which is determined by observation and grading 24 hours and 48 hours after administration.
- Each drug is tested orally by administering a dosage of forty (40) mgm/kgm of body weight to groups of fifteen guinea pigs.
- the appropriate dosage for each animal is packed into a gelatin capsule and placed far back in the animal's pharynx. Swallowing is assisted by syringe delivery of three milliliters of water.
- the animals are not allowed to eat or drink six hours before and after administration of each product.
- the exposure to ultraviolet "A" radiation is at a dose of four joules per square centimeter at different times after administration, e.g., 10, 20, 30, 45, 60, 90, 120, 180, 240 minutes after administration. Readings and evaluations are carried out 48 hours post ingestion. When a particular product is exceptionally active in the test, the per os dosage may of course be halved or otherwise reduced.
- the compounds of the invention show erythematic topical activity as read at both 24 and 48 hours. They show oral activity as read at 48 hours which is outstanding, with high maxima, early onset, and rapid decline in photosensitizing effect.
- the compound 4-methyl-8-aminomethylpsoralen is particularly outstanding, dropping off to no response at 180 minutes, with an early onset of only 10 minutes, reaching a vesicubullous reaction height at only 45 minutes, and dropping off to gradation 1+ at 120 minutes.
- the compound 4'-aminomethyl-4,5',8-trimethylpsoralen shows a high order of oral toxicity, a large number of the animals receiving 40 mgm/kgm thereof dying during the period of their observation, the LD50 for that particular compound apparently being much less than this dosage level.
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Cosmetics (AREA)
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/073,907 US4269851A (en) | 1979-09-10 | 1979-09-10 | 8-Aminoalkyl-4-alkylpsoralens |
IE1891/80A IE50160B1 (en) | 1979-09-10 | 1980-08-09 | 8-aminoalkyl-4-alkylpsoralens |
IT24520/80A IT1132695B (it) | 1979-09-10 | 1980-09-08 | 8-amminoalchil-4-alchilpsoraleni e metodo per la loro produzione |
BE0/202046A BE885156A (fr) | 1979-09-10 | 1980-09-09 | Psoralenes, leur procede de preparation et compositions pharmaceutiques les contenant |
CA000359872A CA1141766A (en) | 1979-09-10 | 1980-09-09 | 8-aminoalkyl-4-alkylpsoralens |
AU62170/80A AU532763B2 (en) | 1979-09-10 | 1980-09-09 | 8-aminoalkyl-4-alkylpsoralens |
NL8005081A NL8005081A (nl) | 1979-09-10 | 1980-09-09 | 8-aminoalkyl-4-alkylpsoralenen. |
AT0453780A AT373258B (de) | 1979-09-10 | 1980-09-09 | Verfahren zum herstellen von neuen 4-alkyl-8aminoalkyl-psoralenen |
GB8029145A GB2058073B (en) | 1979-09-10 | 1980-09-09 | 8-aminoalkyl-4-alkylpsoralens |
DE19803033895 DE3033895A1 (de) | 1979-09-10 | 1980-09-09 | Psoralene, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
SE8006294A SE448237B (sv) | 1979-09-10 | 1980-09-09 | 8-aminoalkyl-4-alkylpsoralener, forfarande for deras framstellning samt farmaceutisk komposition, vilken sasom aktiv komponent innehaller nemnda foreningar |
FR8019451A FR2464957A1 (fr) | 1979-09-10 | 1980-09-09 | Psoralenes, leur procede de preparation et compositions pharmaceutiques les contenant |
CH680880A CH644864A5 (de) | 1979-09-10 | 1980-09-10 | Psoralenderivate, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate. |
JP12474380A JPS5645479A (en) | 1979-09-10 | 1980-09-10 | 88aminoalkyll44alkylpsoralene |
US06/236,765 US4328239A (en) | 1979-09-10 | 1981-02-23 | 8-Aminoalkylpsoralens |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/073,907 US4269851A (en) | 1979-09-10 | 1979-09-10 | 8-Aminoalkyl-4-alkylpsoralens |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/236,765 Continuation-In-Part US4328239A (en) | 1979-09-10 | 1981-02-23 | 8-Aminoalkylpsoralens |
Publications (1)
Publication Number | Publication Date |
---|---|
US4269851A true US4269851A (en) | 1981-05-26 |
Family
ID=22116511
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/073,907 Expired - Lifetime US4269851A (en) | 1979-09-10 | 1979-09-10 | 8-Aminoalkyl-4-alkylpsoralens |
Country Status (14)
Country | Link |
---|---|
US (1) | US4269851A (sv) |
JP (1) | JPS5645479A (sv) |
AT (1) | AT373258B (sv) |
AU (1) | AU532763B2 (sv) |
BE (1) | BE885156A (sv) |
CA (1) | CA1141766A (sv) |
CH (1) | CH644864A5 (sv) |
DE (1) | DE3033895A1 (sv) |
FR (1) | FR2464957A1 (sv) |
GB (1) | GB2058073B (sv) |
IE (1) | IE50160B1 (sv) |
IT (1) | IT1132695B (sv) |
NL (1) | NL8005081A (sv) |
SE (1) | SE448237B (sv) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4328239A (en) * | 1979-09-10 | 1982-05-04 | Elder Pharmaceuticals, Inc. | 8-Aminoalkylpsoralens |
US4370344A (en) * | 1979-09-10 | 1983-01-25 | Elder Pharmaceuticals, Inc. | 5'-Aminoalkyl-4'-alkylpsoralens |
US5116864A (en) * | 1991-04-09 | 1992-05-26 | Indiana University Foundation | Method for preventing restenosis following reconfiguration of body vessels |
US5556993A (en) * | 1993-06-28 | 1996-09-17 | Steritech, Inc. | Compounds for the photodecontamination of pathogens in blood |
US5585503A (en) * | 1993-06-28 | 1996-12-17 | Steritech, Inc. | Compounds for the photodecontamination of pathogens in blood |
US5593823A (en) * | 1993-06-28 | 1997-01-14 | Cerus Corporation | Method for inactivating pathogens in blood using photoactivation of 4'-primary amino-substituted psoralens |
US5871900A (en) * | 1993-06-28 | 1999-02-16 | Cerus Corporation | Method of inactivating pathogens in biological fluids using photoactivated 5-primaryamino psoralens |
WO1999026476A1 (en) * | 1997-11-20 | 1999-06-03 | Cerus Corporation | New psoralens for pathogen inactivation |
US6004741A (en) * | 1993-06-28 | 1999-12-21 | Cerus Corporation | Method for the photoactivation of 4' and 5' primary aminoalkyl psoralens in platelet preparations |
US6004742A (en) * | 1993-06-28 | 1999-12-21 | Cerus Corporation | Method for inactivation of pathogens in platelets using 4' and 5' primary amino-substituted psoralens |
US6143490A (en) * | 1994-11-14 | 2000-11-07 | Cerus Corporation | Treating blood or blood product with a compound having a mustard and a nucleic acid binding moiety |
US6177441B1 (en) | 1995-06-05 | 2001-01-23 | Cerus Corporation | Treating red blood cell solutions with anti-viral agents |
US6686480B2 (en) | 1993-06-28 | 2004-02-03 | Cerus Corporation | Compounds for the photodecontamination of pathogens in blood |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4124598A (en) * | 1976-10-20 | 1978-11-07 | Hoffmann-La Roche Inc. | Psoralens |
US4169204A (en) * | 1976-10-20 | 1979-09-25 | Regents Of The University Of California | Psoralens |
US4217445A (en) * | 1976-05-28 | 1980-08-12 | Fotobio Holding Ag | 5-Oxy-substituted derivatives of Psoralene useful in dermatology |
-
1979
- 1979-09-10 US US06/073,907 patent/US4269851A/en not_active Expired - Lifetime
-
1980
- 1980-08-09 IE IE1891/80A patent/IE50160B1/en unknown
- 1980-09-08 IT IT24520/80A patent/IT1132695B/it active
- 1980-09-09 AU AU62170/80A patent/AU532763B2/en not_active Ceased
- 1980-09-09 FR FR8019451A patent/FR2464957A1/fr active Granted
- 1980-09-09 CA CA000359872A patent/CA1141766A/en not_active Expired
- 1980-09-09 DE DE19803033895 patent/DE3033895A1/de active Granted
- 1980-09-09 NL NL8005081A patent/NL8005081A/nl not_active Application Discontinuation
- 1980-09-09 SE SE8006294A patent/SE448237B/sv not_active IP Right Cessation
- 1980-09-09 AT AT0453780A patent/AT373258B/de not_active IP Right Cessation
- 1980-09-09 GB GB8029145A patent/GB2058073B/en not_active Expired
- 1980-09-09 BE BE0/202046A patent/BE885156A/fr not_active IP Right Cessation
- 1980-09-10 CH CH680880A patent/CH644864A5/de not_active IP Right Cessation
- 1980-09-10 JP JP12474380A patent/JPS5645479A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4217445A (en) * | 1976-05-28 | 1980-08-12 | Fotobio Holding Ag | 5-Oxy-substituted derivatives of Psoralene useful in dermatology |
US4124598A (en) * | 1976-10-20 | 1978-11-07 | Hoffmann-La Roche Inc. | Psoralens |
US4169204A (en) * | 1976-10-20 | 1979-09-25 | Regents Of The University Of California | Psoralens |
Non-Patent Citations (6)
Title |
---|
Dawber, J. Soc. Comet. Chem., 28-403-406, 1977. * |
Hearst et al., (II), Chem. Abst. 87: 78962f, 1977. * |
Isaacs et al., Chem. Abst., 86: 135108n. * |
Johnston et al., Chem. Abst., 87: 147284a. * |
Martins et al., Chem. Abst., vol. 81, 1974, 99676g. * |
Shen et al., Chem. Abst., vol. 88, 88: 59494j. * |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4328239A (en) * | 1979-09-10 | 1982-05-04 | Elder Pharmaceuticals, Inc. | 8-Aminoalkylpsoralens |
US4370344A (en) * | 1979-09-10 | 1983-01-25 | Elder Pharmaceuticals, Inc. | 5'-Aminoalkyl-4'-alkylpsoralens |
US5116864A (en) * | 1991-04-09 | 1992-05-26 | Indiana University Foundation | Method for preventing restenosis following reconfiguration of body vessels |
US6004741A (en) * | 1993-06-28 | 1999-12-21 | Cerus Corporation | Method for the photoactivation of 4' and 5' primary aminoalkyl psoralens in platelet preparations |
US6017691A (en) * | 1993-06-28 | 2000-01-25 | Cerus Corporation | 4'-primary aminopsoralen and platelet compositions |
US5593823A (en) * | 1993-06-28 | 1997-01-14 | Cerus Corporation | Method for inactivating pathogens in blood using photoactivation of 4'-primary amino-substituted psoralens |
US5625079A (en) * | 1993-06-28 | 1997-04-29 | Cerus Corporation | Synthesizing psoralen compounds useful as intermediates |
US5654443A (en) * | 1993-06-28 | 1997-08-05 | Cerus Corporation | Compounds for the photo decontamination of pathogens in blood |
US5712085A (en) * | 1993-06-28 | 1998-01-27 | Cerus Corporation | 5'-(4-amino-2-oxa)butye-4,4', 8-trinethylpsoralen in synthetic medium |
US5871900A (en) * | 1993-06-28 | 1999-02-16 | Cerus Corporation | Method of inactivating pathogens in biological fluids using photoactivated 5-primaryamino psoralens |
US6686480B2 (en) | 1993-06-28 | 2004-02-03 | Cerus Corporation | Compounds for the photodecontamination of pathogens in blood |
US5972593A (en) * | 1993-06-28 | 1999-10-26 | Cerus Corporation | Method for the photo-decontamination of pathogens in blood using 4'-primary amino psoralens |
US5556993A (en) * | 1993-06-28 | 1996-09-17 | Steritech, Inc. | Compounds for the photodecontamination of pathogens in blood |
US6004742A (en) * | 1993-06-28 | 1999-12-21 | Cerus Corporation | Method for inactivation of pathogens in platelets using 4' and 5' primary amino-substituted psoralens |
US5585503A (en) * | 1993-06-28 | 1996-12-17 | Steritech, Inc. | Compounds for the photodecontamination of pathogens in blood |
US6503699B1 (en) | 1993-06-28 | 2003-01-07 | Cerus Corporation | Method for photodecontamination of pathogens in blood using 5'-primary aminopsoralens |
US6469052B2 (en) | 1993-06-28 | 2002-10-22 | Cerus Corporation | Compounds for the photodecontamination of pathogens in blood |
US6218100B1 (en) | 1993-06-28 | 2001-04-17 | Cerus Corporation | 5′-primary aminoalkyl psoralen compositions with platelets |
US6194139B1 (en) | 1993-06-28 | 2001-02-27 | Cerus Corporation | Methods for photodecontamination of pathogens in blood |
US6171777B1 (en) | 1994-11-14 | 2001-01-09 | Cerus Corporation | Treating blood or blood product with a compound having a mustard and a nucleic acid binding moiety |
US6410219B1 (en) | 1994-11-14 | 2002-06-25 | Cerus Corporation | Treating blood or blood products with compounds which have a mustard, azirdinium or aziridine group and a nucleic acid binding group |
US6143490A (en) * | 1994-11-14 | 2000-11-07 | Cerus Corporation | Treating blood or blood product with a compound having a mustard and a nucleic acid binding moiety |
US20020182581A1 (en) * | 1994-11-14 | 2002-12-05 | Cerus Corporation | Treating blood or blood products with compounds which have a mustard, aziridinium or aziridine group and a nucleic acid binding group |
US6177441B1 (en) | 1995-06-05 | 2001-01-23 | Cerus Corporation | Treating red blood cell solutions with anti-viral agents |
US6455286B1 (en) | 1997-11-20 | 2002-09-24 | Cerus Corporation | Psoralens for pathogen inactivation |
US6133460A (en) * | 1997-11-20 | 2000-10-17 | Cerus Corporation | Psoralens for pathogen inactivation |
WO1999026476A1 (en) * | 1997-11-20 | 1999-06-03 | Cerus Corporation | New psoralens for pathogen inactivation |
Also Published As
Publication number | Publication date |
---|---|
IT1132695B (it) | 1986-07-02 |
NL8005081A (nl) | 1981-03-12 |
JPS5645479A (en) | 1981-04-25 |
CH644864A5 (de) | 1984-08-31 |
GB2058073A (en) | 1981-04-08 |
DE3033895A1 (de) | 1981-04-02 |
GB2058073B (en) | 1983-06-08 |
DE3033895C2 (sv) | 1989-04-20 |
CA1141766A (en) | 1983-02-22 |
AU6217080A (en) | 1981-03-19 |
FR2464957A1 (fr) | 1981-03-20 |
AU532763B2 (en) | 1983-10-13 |
BE885156A (fr) | 1980-12-31 |
SE8006294L (sv) | 1981-03-11 |
IT8024520A0 (it) | 1980-09-08 |
FR2464957B1 (sv) | 1982-12-03 |
IE50160B1 (en) | 1986-02-19 |
IE801891L (en) | 1981-03-10 |
SE448237B (sv) | 1987-02-02 |
AT373258B (de) | 1984-01-10 |
ATA453780A (de) | 1983-05-15 |
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